1. Field of the Invention
The present invention relates to a novel physiologically active substance, more particularly, to a physiologically active complex having an activity of tumor necrosis factor (abbreviated as TNF hereinafter).
2. Description of the Prior Art
As described in “The Cytokine Handbook”, 2nd edition, edited by Angus Thomson, published by Academic Press, pp. 289–304 (1994) TNF was first discovered by L. J. Old et al. in 1975 as a cytotoxic factor secreted in serum of animals such as rabbits and mice when sequentially administered with BCG and bacterial toxin. Later studies revealed that TNF is a protein having a molecular weight of about 17,000 daltons and an isoelectric point of 5.6, produced mainly by macrophages.
From the beginning of the discovery, TNF has been highly focused on its use as a medicament for malignant tumors and developed for such purposes due to its selective cytotoxic action on tumor cells, as disclosed in Japanese Patent Kokoku Nos. 45,208/87 and 46,928/92. However, when intravenously administered to living bodies, TNF is promptly decomposed by protease in the blood or excreted into urine within a relatively short period of time so that TNF could not be kept at the desired blood level for a relatively long period of time. While, an increased amount of TNF administration to subjects to higher the blood level of TNF would affect even normal cells due to the cytotoxic action by TNF.